Wednesday, September 17, 2008

vittamin D, again

See post under "lab tests."

2 comments:

dogdoc said...

Vitamen D and immunity- what a research can of worms to open! More on that in a minute.

On Singulair- haven't seen enough effect to be clinically applicable, more of a gee whiz. Had been thinking more of a feedback higher up in cascade affecting both arms, but Babs makes sense in that arm.

On med reactions- have seen a severe herx like reaction to statins which I found a reference to in yet another blog. You are a busy guy doc! By the way, I think the book is a great idea.

On Vitamen D, in the end after much more reading, I'm not sure I know much more than I did before (had already read your May post and had done a bunch of research back when I was in MS land). Or at least nothing clinically useful. More like a whole lot more questions.

Vitamin D dysregulation in chronic bacterial and immune disease seems well documented. It is documented in older studies showing low DOH25 levels and newer ones showing low DOH25/ high 1,25(OH)2D. The documentation is spread across a wide variety of research orientations across the world.

Vitamin D is indeed a steroid hormone with similar structure to Cortisol, Testosterone, Estradiol, Progesterone, and Aldosterone. The active form 1,25(OH)2D has DNA binding receptors everywhere including in pretty much all cells involved in immune sytem. There is evidence of competitive binding between the steroids at receptors sites and most of the others have their own binding sites in immune related areas. Chronic dz patients incl bacterial and autoimmune often have multiple endocrine axes effected (good broad based evidence). A big can of worms.

Certainly, vitamin D is a hot spot of current immune research. There is much evidence to support alterations in immunity including decreased TH1 axis and cytokines. However, the research findings are varied and situational with many effects to the contrary. I like the Vitamin D effects depend on the activation and differentiation status of the immune cells thinking.

Trevor Marshalls works are interesting although not necessarily in application. In theory, I was with him fine until the bacterial antagonist of VDR transcription which was sounding plausible until you really think about it. Wouldn't that create the opposite effect and increase complement activated phagocytosis via Th1 arm?

The thing I found most interesting about Marshalls work was the "suprising comorbity of neuro signs" in his original work.

It certainly makes sense as a possible explanation for the conversion to Lforms and hiding out in phagocytic vessicles in immune cells. However, I think the research is being stretcheeeeed a bit to support that conclusion.

Vitamen D supplementation makes zero sense on one level- nor does glucocorticoid use or sex hormone supplementation or any other steroid hormone. Immunosupressives wouldn't make sense in helping fight a chronic bacterial condition. And certainly supressing immunity could create a temporary improvement of signs. HOWEVER, many of the other conditons being bantered around include autoimmunity so not sure where to take that one. Get my drift?

Messing around with the immune system when you doen't know what you are doing has many prominant examples of disasterous consequences. Even it it sounds benign like a "vitamin or natural supplement". Another can of worms.

While it would make sense that some patients might show clinical benefit of decreasing vitamen D activation in the kidney (ie Benicar), here is where clinical science and understanding what is behind it diverge. This is typical of doctoring- have to figure out a way to fix stuff and extrapolate best you can from available evidence. Activated macrophages without intracellular L forms also convert DOH25 to 1,25(OH)2D and this matures monocytes into lines of macrophages in TH1 response. Vitamin D is active is many types of cell maturation. Dysregulation of Vitamen D could have multiple factors and confuse our clinical applications. More cans of worms.

If indeed, we are seeing a true clinical toxicity, where is the hypercalcemia? Is PTH being blocked in this phenomenon and it is not as simple as cause and effect?

It is like trying to figure out a complex, 3D, interactive puzzle with only a handful of pieces and trying to rely on what the extrapolation of pieces inbetween might be.

Argggggh.

dogdoc said...

See what you did? Vitamin D led to full exploration of neuro-endocrine-immune axis.
Final opinion- Benicar it is. 1,25 (OH)2D3 promotes IL-10 production and other factors in TH2 stimulated immune imbalance/ immunosupression.